Cancer of the prostate is a major clinical problem with the diagnosis of 244,000 new cases and more than 40,500 deaths of American men predicted by the American Cancer Society in 1995. Currently, the predicted lifetime incidence of prostate cancer is 15% and the estimated lifetime death risk from this disease is approximately 3.4%. It is not possible by present technologies to distinguish between cancers that will become clinically aggressive versus indolent cancers that will remain clinically benign. Current treatment protocols, including hormonal therapy, radiation therapy and surgery have limitations. Hormonal therapy requires a hormone-responsive tumor; when a tumor develops hormone-insensitivity it can progress unchecked. Attempts at cure using radiation therapy and surgery are limited to eradication of the primary tumors. However, tumor can escape surgical or radiotherapeutic ablation, and these approaches cannot be used to successfully cure, and rarely even to limit metastatic disease. In addition, even when successful, these approaches can significantly diminish the patient""s quality of life. These findings emphasize the need for improved diagnostic and therapeutic approaches for identifying prostate carcinomas, predicting clinical aggressiveness and effectively treating patients with this cancer.
Identifying the genetic elements mediating prostate cancer development and progression will lead to improved diagnostic tests and may ultimately result in gene-, immunological- and drug-based technologies with therapeutic applications. Transfection of human prostate carcinoma (LNCaP) DNA into a new DNA acceptor cell line, CREF-Trans 6, and injection into nude mice results in tumor formation (Su et al., Anticancer Res. 12:297-304, 1992). Using tumor-derived CREF-Trans 6 cells and differential RNA display, the new putative oncogene, prostate tumor inducing gene-1 (PTI-1), has been identified (Shen et al., PNAS 92: 6788-6782, 1995). PTI-1 encodes a mutated and truncated human elongation factor-1xcex1 (EF-1xcex1). Normal EF-1xcex1 plays a prominent role in protein translation, a process that is critical in controlling gene expression and regulating cell growth. PTI-1 expression is observed in human prostate cancer cell lines (LNCaP, DU-145 and PC-3) and patient-derived prostate carcinoma tissue samples (14 of 15), but not in normal prostate (6) or BPH (4) tissue. This observation suggests that PTI-1 expression may be related specifically to carcinoma development. In addition, the observation that PTI-1 expression also occurs in a high proportion of carcinoma cell lines of the breast, colon and lung indicates that this genetic alteration may be a common event in carcinogenesis. If the modified EF-1xcex1 protein encoded by PTI-1 inhibits the ability of normal EF-1xcex1 to proofread mistakes in gene expression that mediate altered protein structure, then PTI-1 may function as a major contributor to the mutator phenotype in specific human cancers. This putative aberrant processing resulting from PTI-1 expression has been termed xe2x80x9ctranslational infidelityxe2x80x9d. If this hypothesis is validated experimentally, altered protein translation would represent a new and novel mechanism underlying cancer development and progression.
Targeted inhibition of PTI-1, using genetic and/or drug interventional approaches, might therefore provide the basis for a novel strategy for the therapy of prostate cancer.
This invention provides a method for reversing cancer phenotype of a cancer cell which comprises introducing a molecule capable of specifically recognizing a Prostate Tumor Inducing Gene into the cell under conditions permitting inhibition of the expression of said gene so as to thereby reverse the cancer phenotype of the cell.
This invention also provides a method for reversing cancer phenotype of a cancer cell in a subject which comprises introducing a molecule capable of specifically recognizing a Prostate Tumor Inducing Gene into the subject""s cancer cell under conditions permitting inhibition of the expression of said gene in the subject""s cell so as to thereby reverse the cancer phenotype of the cell.
This invention provides a method for reversing cancer phenotype of a cancer cell which comprises introducing a compound capable of specifically recognizing the RNA of a Prostate Tumor Inducing Gene into the cell under conditions permitting inhibition of the expression of said RNA so as to thereby reverse the cancer phenotype of the cell.
This invention also provides a method for reversing cancer phenotype of a cancer cell in a subject which comprises introducing a compound capable of specifically recognizing the RNA of a Prostate Tumor Inducing Gene into the subject""s cancer cell under conditions permitting inhibition of the expression of said RNA in the subject""s cell so as to thereby reverse the cancer phenotype of the cell.
This invention provides a method for reversing cancer phenotype of a cancer cell which comprises introducing a substance capable of specifically recognizing the gene product of a Prostate Tumor Inducing Gene into the cell under conditions permitting inhibition of the function of said gene product so as to thereby reverse the cancerous phenotype of the cell.
This invention provides a method for reversing cancer phenotype of a cancer cell in a subject which comprises introducing a substance capable of specifically recognizing the gene product of a Prostate Tumor Inducing Gene into the subject""s cancer cell under conditions permitting inhibition of the function of said gene product in the subject""s cell so as to thereby reverse the cancer phenotype of the cell.